Since the isolation and structural elucidation of natural .beta.-lactamase inhibitor clavulanic acid, a number of naturally occurring metabolites, G0069A (JP 61-212587), Tu 1718 (DE 3727651 A1), Clavamycin (J. of Antibiotic 39, 510 (1986)), Ibid 39, 516 (1986)), Ro 22-5417 (J. of Antibiotic 36, 217 (1983)) have been isolated from the culture of genius streptomyces. None of the above metabolites exhibited .beta.-lactamase inhibitory properties. However, in most cases, attention was paid to their antibacterial and antifungal activity.
We paid attention to develop G0069A (JP 61-212587) as antitumor agent. However, there were a lot of difficulties in obtaining this compound in large scale. For example, only 20 mg of G0069A was isolated from 10L of fermentation broth even after being under well controlled fermentation technique and suitable experimental conditions.
G0069A is a chemicalyl unstable isolation process and required very complex and special techniques. This should be done in the dark at low temperatures. In addition to the above complexity in isolation of G0069A from fermentation broth, the synthetic approach also seemed to be an extremely difficult multi-step process because they have 5-asymmetric carbon centres and dipeptide side chain. Therefore, it is necessary to get compounds which are relatively easy to synthesize, have shorter chains than G0069A, chemically stable and have stronger antitumor activity.